Limits...
Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma.

Liu P, Sun L, Zhou DS, Zhang P, Wang YH, Li D, Li QH, Feng RJ - Sci Rep (2015)

Bottom Line: PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP.PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%).The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.

ABSTRACT
In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma.

No MeSH data available.


Related in: MedlinePlus

In vivo antitumor efficacy of free CDDP and PLD/CDDP in MG-63 cancer cell bearing tumor xenograft model.The mice were injected with cancer cell on the right flank and the treatment was started when the tumor volume reached ~100 mm3. The formulations were intravenously administered 4 times during first 12 days and tumor volume was measured using vernier caliper. (a) Tumor volume (b) body weight index. Data are expressed as standard deviation of the mean and n = 8. *p < 0.05 and **p < 0.01 is the statistical difference between tumor volume of CDDP and CDDP/PLD treated group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4664968&req=5

f6: In vivo antitumor efficacy of free CDDP and PLD/CDDP in MG-63 cancer cell bearing tumor xenograft model.The mice were injected with cancer cell on the right flank and the treatment was started when the tumor volume reached ~100 mm3. The formulations were intravenously administered 4 times during first 12 days and tumor volume was measured using vernier caliper. (a) Tumor volume (b) body weight index. Data are expressed as standard deviation of the mean and n = 8. *p < 0.05 and **p < 0.01 is the statistical difference between tumor volume of CDDP and CDDP/PLD treated group.

Mentions: In vivo antitumor efficacy of different formulations was investigated in MG-63 cancer cell bearing xenograft tumor model. As seen from Fig. 6, tumor volume constantly expanded from ~100 mm3to ~2300 mm3at the end of 24 days in the untreated mice group. Consistently, tumor volume gradually increased in the blank NP treated group indicating that material comprising the vector barely had physiological activity (~2250 mm3). Free CDDP exhibited considerable tumor inhibiting capacity with final tumor volume of ~1400 mm3. The obvious delay in the tumor growth was mainly attributed to the strong antitumor effect of CDDP in the xenograft model. Among all the mice groups, PLD/CDDP exhibited a most significant (p < 0.01) anti-tumor activity with maximum tumor growth inhibition. The final tumor volume in PLD/CDDP treated group was ~700 mm3 indicating its superior anticancer efficacy in osteosarcoma. The superior antitumor effect of PLD/CDDP was attributed to the sustained release of drug from the nanosystem, possible enhanced tumor distribution of drugs, and induction of cell apoptosis2930.


Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma.

Liu P, Sun L, Zhou DS, Zhang P, Wang YH, Li D, Li QH, Feng RJ - Sci Rep (2015)

In vivo antitumor efficacy of free CDDP and PLD/CDDP in MG-63 cancer cell bearing tumor xenograft model.The mice were injected with cancer cell on the right flank and the treatment was started when the tumor volume reached ~100 mm3. The formulations were intravenously administered 4 times during first 12 days and tumor volume was measured using vernier caliper. (a) Tumor volume (b) body weight index. Data are expressed as standard deviation of the mean and n = 8. *p < 0.05 and **p < 0.01 is the statistical difference between tumor volume of CDDP and CDDP/PLD treated group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664968&req=5

f6: In vivo antitumor efficacy of free CDDP and PLD/CDDP in MG-63 cancer cell bearing tumor xenograft model.The mice were injected with cancer cell on the right flank and the treatment was started when the tumor volume reached ~100 mm3. The formulations were intravenously administered 4 times during first 12 days and tumor volume was measured using vernier caliper. (a) Tumor volume (b) body weight index. Data are expressed as standard deviation of the mean and n = 8. *p < 0.05 and **p < 0.01 is the statistical difference between tumor volume of CDDP and CDDP/PLD treated group.
Mentions: In vivo antitumor efficacy of different formulations was investigated in MG-63 cancer cell bearing xenograft tumor model. As seen from Fig. 6, tumor volume constantly expanded from ~100 mm3to ~2300 mm3at the end of 24 days in the untreated mice group. Consistently, tumor volume gradually increased in the blank NP treated group indicating that material comprising the vector barely had physiological activity (~2250 mm3). Free CDDP exhibited considerable tumor inhibiting capacity with final tumor volume of ~1400 mm3. The obvious delay in the tumor growth was mainly attributed to the strong antitumor effect of CDDP in the xenograft model. Among all the mice groups, PLD/CDDP exhibited a most significant (p < 0.01) anti-tumor activity with maximum tumor growth inhibition. The final tumor volume in PLD/CDDP treated group was ~700 mm3 indicating its superior anticancer efficacy in osteosarcoma. The superior antitumor effect of PLD/CDDP was attributed to the sustained release of drug from the nanosystem, possible enhanced tumor distribution of drugs, and induction of cell apoptosis2930.

Bottom Line: PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP.PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%).The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.

ABSTRACT
In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma.

No MeSH data available.


Related in: MedlinePlus